Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells

X. Guo1, J.E. Seo1, S.M. Bryce2, J.A. Tan1, Q. Wu1, S.L. Dial1, M.M. Moore1, N. Mei1

1 National Center for Toxicological Research, US Food and Drug Administration
2 Litron Laboratories

Toxicological Sciences
Volume 163, Issue 1, 1 May 2018, Pages 214–225

TEMPO and similar compounds have a wide range of uses, from radioprotection to treatment of hypertension, glaucoma, and cancer. The toxic effects of these compounds, however, are not well understood.
Recently, TEMPO has been found to be mutagenic in vitro. Further testing was performed in order to understand the potential genotoxicity of TEMPO and three of its derivatives. Because of the variations in chemical structure, these compounds can have different levels of effectiveness and toxicity. Interestingly, previous testing has shown paradoxical mutagenic and cytotoxic results.
Working in TK6 cells, Litron’s MultiFlow DNA Damage Kit (p53, yH2AX, phospho-histone H3) was used to evaluate the clastogenic, aneugenic or non-genotoxic properties of these compounds. 
Data from this work were evaluated using both Global Evaluation Factors and Machine Learning algorithms. Both approaches clearly showed a high likelihood that TEMPO and all three of its derivatives have a clastogenic Mode of Action (MoA).